Welcome to Scholar Publishing Group

International Journal of Health and Pharmaceutical Medicine, 2023, 4(1); doi: 10.38007/IJHPM.2023.040116.

Rhein Improves Sepsis Rats by Reducing Inflammatory Reaction and Regulating AQP2 Acute Renal Injury


Chao Liu, Nannan Song, Rui Yao, Xiaoju Zhang, Xiaojing Dong and Feng Li

Corresponding Author:
Feng Li

Xijing Hospital, Xi’an 710032, Shaanxi, China


Background: Inflammation is a typical manifestation of sepsis related acute renal injury. AQP2 is considered to play an important role in renal fluid transport. This study aims to explore whether rhein has a protective effect on renal injury and its potential mechanism. Methods: A sepsis rat model of acute renal injury was established. 60 SD rats were randomly divided into control group, model group, high rhein (200mg/kg), medium rhein (100mg/kg), low dose rhein (50mg/kg) and dexamethasone group. Observe the general condition of rats and detect serum creatinine (Scr), blood urea nitrogen (BUN) and TNF – α, IL-1 β, IL-10 expression; H&E staining was used to observe the pathological morphology of rat kidney; Immunofluorescence method was used to detect the expression of AQP2 in renal tissue: Western Blot method was used to detect the changes of protein expression of AQP2, NF-KB, P-NF-KB, IKB-α,P- IKB-α in renal tissue. Results: Compared with the control group, the levels of serum Scr, BUN and TNF- α, IL-1 β,and the level of IL-10 was significantly increased. There were obvious swelling of renal tubules, necrosis and abscission of epithelial cells of renal tubules, edema of renal interstitium, infiltration of inflammatory cells and other pathological damages in renal tissues; Compared with the model group, the rat serum Scr, BUN levels, TNF- α, IL-1β and the level of IL-10 was significantly reduced, and the pathological damage of renal tissue was significantly reduced. Conclusion: Rhein can reduce the inflammatory reaction, increase the expression of AQP2, and improve the acute renal injury in septic rats.


Acute Renal Injury, Rhein Acid, Inflammation, Aquaporin 2

Cite This Paper

Chao Liu, Nannan Song, Rui Yao, Xiaoju Zhang, Xiaojing Dong and Feng Li. Rhein Improves Sepsis Rats by Reducing Inflammatory Reaction and Regulating AQP2 Acute Renal Injury. International Journal of Health and Pharmaceutical Medicine (2023), Vol. 4, Issue 1: 156-163. https://doi.org/10.38007/IJHPM.2023.040116.


[1] Sato, Y. and Yanagita, M. (2018) Immune cells and inflammation in AKI to CKD progression. Am J Physiol Renal Physiol. Dec 1; 315(6):F1501-F1512. https://doi.org/10.1152/ajprenal.00195.2018

[2] Singbartl, K. and Kellum, J.A. (2012) AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int. May; 81(9):819-25. https://doi.org/10.1038/ki.2011.339

[3] Peerapornratana, S., Manrique-Caballero, C.L., Gómez, H. and Kellum, J.A. (2019) Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int. Nov; 96(5):1083-1099. https://doi.org/10.1016/j.kint.2019.05.026

[4] Yoo, J.Y., Cha, D.R., Kim, B., An, E.J., Lee, S.R., Cha, J.J., Kang, Y.S., Ghee, J.Y., Han, J.Y. and Bae, Y.S. (2020) LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1. Cell Rep. Oct 20; 33(3):108245. https://doi.org/10.1016/j.celrep.2020.108245

[5] Hao, K., Qi, Q., Wan, P., Zhang, J., Hao, H., Liang, Y., Xie, L., Wang, G. and Sun, J. (2014) Prediction of human pharmacokinetics from preclinical information of rhein, an antidiabetic nephropathy drug, using a physiologically based pharmacokinetic model. Basic Clin Pharmacol Toxicol. Feb; 114(2):160-7. https://doi.org/10.1111/bcpt.12148

[6] Zeng, C.C., Liu, X., Chen, G.R., Wu, Q.J., Liu, W.W., Luo, H.Y. and Cheng, J.G. (2014) The molecular mechanism of rhein in diabetic nephropathy. Evid Based Complement Alternat Med, 487097 https://doi.org/10.1155/2014/487097

[7] Zhu, Y., Yang, S., Lv, L., Zhai, X., Wu, G., Qi, X., Dong, D. and Tao, X. (2022) Research Progress on the Positive and Negative Regulatory Effects of Rhein on the Kidney: A Review of Its Molecular Targets. Molecules. Oct 4; 27(19):6572. https://doi.org/10.3390/molecules27196572

[8] Su, W., Cao, R., Zhang, X.Y. and Guan Y. (2020) Aquaporins in the kidney: physiology and pathophysiology. Am J Physiol Renal Physiol. Jan 1; 318(1):F193-F203. https://doi.org/10.1152/ajprenal.00304.2019

[9] Wang, Y., Zhang, W., Yu, G., Liu, Q. and Jin, Y. (2018) Cytoprotective effect of aquaporin 1 against lipopolysaccharide-induced apoptosis and inflammation of renal epithelial HK-2 cells. Exp Ther Med. May; 15(5):4243-4252. https://doi.org/10.3892/etm.2018.5992

[10] Rump, K. and Adamzik, M. (2018) Function of aquaporins in sepsis: a systematic review. Cell Biosci. Feb 9; 8:10. https://doi.org/10.1186/s13578-018-0211-9

[11] He, J. and Yang, B. (2019) Aquaporins in Renal Diseases. Int J Mol Sci. Jan 16; 20(2):366. https://doi.org/10.3390/ijms20020366

[12] Wang, R., Wu, S.T., Yang, X., Qian, Y., Choi, J.P., Gao, R., Song, S., Wang, Y., Zhuang, T., Wong, J.J., Zhang, Y., Han, Z., Lu, H.A., Alexander, S.I., Liu, R., Xia, Y. and Zheng, X. (2021) Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting. JCI Insight. Jun 22; 6(12):e142838. https://doi.org/10.1172/jci.insight.142838

[13] Liang, C.L., Zhang, P.C., Wu, J.B., Liu, B.H., Yu, H., Lu, R.R., Jie, Z. and Zhou, J.Y. (2019) Zhen-wu-tang attenuates Adriamycin-induced nephropathy via regulating AQP2 and miR-92b. Biomed Pharmacother. Jan; 109:1296-1305. https://doi.org/10.1016/j.biopha.2018.10.146

[14] Brandoni, A. and Torres, A.M. (2021) Renal expression and urinary excretion of aquaporin-2 in postobstructive uropathy in rats. Can J Physiol Pharmacol. Jun; 99(6):619-626. https://doi.org/10.1139/cjpp-2020-0481

[15] Foo, S.Y. and Nolan, G.P. (1999) NF-kappaB to the rescue: RELs, apoptosis and cellular transformation. Trends Genet. Jun; 15(6):229-35. https://doi.org/10.1016/S0168-9525(99)01719-9 

[16] Ghosh, S., May, M.J. and Kopp, E.B. (1998) NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 16:225-60. https://doi.org/10.1146/annurev.immunol.16.1.225